Biomedical subjects

J P Aggleton

Publications and source records attributed to J P Aggleton.

At least 37 records · Page 2Linked to original sources

PubMed2000

Distinct patterns of behavioural impairments resulting from fornix transection or neurotoxic lesions of the perirhinal and postrhinal cortices in the rat.

The present study provides evidence that lesions of the fornix (FNX) and of the perirhinal/postrhinal cortex (PPRH), which both disconnect the hippocampus from other brain regions, can lead to distinct patterns of behavioural impairments on tests of spatial memory and spontaneous object recognition. For example, whereas FNX lesions impaired allocentric spatial delayed alternation in a T-maze but generally spared a test of spontaneous object recognition, PPRH lesions produced the opposite pattern of results. Indeed, on the T-maze task PPRH animals significantly outperformed controls when the retention delay was increased to 60 s. In addition, some evidence was found that contributions from both the fornix and perirhinal/postrhinal cortex may be required when object and spatial information must be integrated. In an object-in-place test, for example, PPRH animals failed according to two measures, and FNX animals failed according to one measure, to discriminate objects that had remained in fixed locations from those that had exchanged locations with other objects. Neither lesion, however, affected performance of a visuospatial conditional task, a Pavlovian autoshaping task, or a one-pair pattern discrimination task. It is suggested that the perirhinal/postrhinal cortex, rather than being specialised for a particular type of associative learning, is important for processing complex visual stimuli.

Animals↗

PubMed2000

Fos imaging reveals differential patterns of hippocampal and parahippocampal subfield activation in rats in response to different spatial memory tests.

We compared neuronal activation, as measured by Fos staining, during different spatial tasks in two experiments. The counts of Fos-stained neurons in the hippocampus increased as the spatial demands of the tasks increased, the tasks having been carefully matched for other factors. In Experiment 1, matched groups of rats either ran a standard eight-arm radial maze task or were trained to run up and down just one arm of the maze; the number of runs and rewards was identical in both conditions. In Experiment 2, rats were trained on the eight-arm maze but in different rooms. On the critical test day, both groups were run in the same room so that one group now performed with novel landmarks. All hippocampal subfields (dentate gyrus, CA3, CA1, dorsal, ventral, and caudal subiculum) showed a relative increases in c-fos activation in the eight-arm (Experiment 1) and novel room (Experiment 2) conditions, the sole exception being the ventral subiculum in Experiment 2. Although increased c-fos activation was found in both dorsal and ventral hippocampus, in Experiment 2 the relative increase was significantly greater in the dorsal hippocampus. Parahippocampal cortices responded heterogeneously: the perirhinal cortex failed to show increased activation in both experiments, in contrast to the entorhinal and postrhinal cortices. Subsequent comparisons confirmed that the perirhinal and postrhinal cortices responded in qualitatively different ways, the perirhinal cortex differing from the rest of the hippocampal formation. These experiments, which provide the first analysis of hippocampal Fos production during tests of allocentric spatial working memory, reveal that all components of the hippocampus are activated, but that under certain conditions the dorsal hippocampus is disproportionately involved.

Animals↗

PubMed2000

Identifying cortical inputs to the rat hippocampus that subserve allocentric spatial processes: a simple problem with a complex answer.

A consideration of the cortical projections to the hippocampus provides a number of candidate regions that might provide distal sensory information needed for allocentric processing. Prominent among the input regions are the entorhinal cortex, the perirhinal cortex, the postrhinal cortex, and the retrosplenial cortex. A review of these sites reveals the surprising fact that in spite of their anatomical connections, removal of the perirhinal and postrhinal cortices has little or no effect on spatial tasks and hence does not functionally disconnect the hippocampus. Extensive retrosplenial lesions have only mild effects, and even lesions of the entorhinal cortex only partially mimic the effects of hippocampal lesions upon tests of spatial memory. In contrast, studies using c-fos imaging support the involvement of the entorhinal, postrhinal, and retrosplenial cortices, but not the perirhinal cortex. It is argued that there exist multiple aspects of spatial memory, and this is reflected in the multiple routes by which cortical information can reach the hippocampus. One consequence is that lesions in a single site often have surprisingly mild effects on standard spatial tests.

Afferent Pathways↗

PubMed2000

Intact negative patterning in rats with fornix or combined perirhinal and postrhinal cortex lesions.

It has been proposed that the hippocampal formation is necessary for the acquisition of tasks that require the use of configural representations for their solution, including spatial learning and negative patterning. Tests of this influential view have, however, yielded conflicting results. For example fornix or hippocampal lesions, which reliably impair spatial learning, do not reliably impair negative patterning. A problem in interpreting these results has been the lack of controls for factors such as over-responding, excitatory effects of reward, and the possibility of non-configural solutions. At the same time, other studies have pointed to a role in configural learning for parahippocampal regions such as the perirhinal cortex. The present experiments controlled for the above factors and revealed that neither lesions of the fornix nor of the perirhinal/postrhinal cortex in the rat had any effect on negative patterning, although subsequent tests of object and spatial memory demonstrated the functional efficacy of the lesions.

Amygdala↗

PubMed2000

The functional anatomy of visual-tactile integration in man: a study using positron emission tomography.

The integration of neural signals from different sensory modalities is a prerequisite for many cognitive and behavioural functions. In this study, we have mapped the functional anatomy of the integration of sensory signals across the tactile and visual modalities. Using the PET radiotracer H2(15)O, regional cerebral blood flow (rCBF) changes were measured in eight normal volunteers performing crossmodal recognition of simultaneously presented visual and tactile stimuli using a modified version of the 'arc-circle test'. Whilst intramodal matching within the visual modality led to relative rCBF increases in the visual association cortex, crossmodal matching (visual-tactile), when compared to intramodal matching, was accompanied by relative rCBF increases in the anterior cingulate cortex, inferior parietal lobules, the left dorsolateral prefrontal cortex (DLPFC) and the left claustrum/insular cortex. The pattern of brain activation is congruent with areas of heteromodal and supramodal cortex and indicates that activation of multimodal areas is required to solve the crossmodal problem.

Adult↗

PubMed2000

A comparison of egocentric and allocentric spatial memory in a patient with selective hippocampal damage.

The spatial memory of a single patient (YR) was investigated. This patient, who had relatively selective bilateral hippocampal damage, showed the pattern of impaired recall but preserved item recognition on standardised memory tests that has been suggested by Aggleton and Shaw [Aggleton JP, Shaw C. Amnesia and recognition memory: a reanalysis of psychometric data. Neuropsychologia 1996;34:51-62] to be a consequence of Papez circuit lesions. YR was tested on three recall tests and one recognition test for visuospatial information. The initial recall test assessed visuospatial memory over very short unfilled delays and YR was not significantly impaired. This test was then modified to test recall of allocentric and egocentric spatial information separately after filled delays of between 5 and 60 s. YR was found to be more impaired at recalling allocentric than egocentric information after a 60 s interval with a tendency for the impairment to increase up to this delay. Recognition of allocentric spatial information was also assessed after delays of 5 and 60 s. YR was impaired after the 60 s delay. The results suggest that the human hippocampus has a greater involvement in allocentric than egocentric spatial memory, and that this most likely concerns the consolidation of allocentric information into long-term memory rather than the initial encoding of allocentric spatial information. The findings also suggest that YR's item recognition/free recall deficit pattern reflects a problem retrieving or storing certain kinds of associative information.

Brain Mapping↗

PubMed2000

Fos expression in the rostral thalamic nuclei and associated cortical regions in response to different spatial memory tests.

Using the quantification of the Fos protein as an indicator of neuronal activation, we studied the involvement of the rostral thalamic nuclei and associated structures in different spatial memory tasks in two experiments. In both experiments, tasks were matched for sensorimotor factors but differed in their spatial and mnemonic demands. In Experiment 1, matched groups of rats either ran in a standard eight-arm radial maze or ran up and down just one arm of the maze while the number of runs and rewards were matched across pairs of rats. In Experiment 2, both groups were trained on the eight-arm radial maze but in different rooms. On the test day, one group was moved so that both groups now performed the same radial-maze task in the same room but for one group the extramaze cues were novel. There were significant increases in Fos in all three of the anterior thalamic nuclei (anterodorsal, anteroventral and anteromedial) as well as the adjacent nucleus reuniens and rostral reticular thalamic nucleus, in both the eight-arm versus one-arm condition (Experiment 1) and the novel room versus familiar room condition (Experiment 2). There were no significant differences in the mediodorsal thalamic nucleus in either experiment. The more spatially demanding task in each experiment also resulted in increased Fos expression in the subicular complex (postsubiculum, presubiculum and parasubiculum), as well as in the prelimbic cortex. Performing the standard radial-arm maze task also produced significant Fos increases in both rostral and caudal levels of the retrosplenial cortex when compared to rats running up and down a single arm in the same maze (Experiment 1); performing the task in a novel room did not, however, result in any further Fos increases in this region (Experiment 2). The specificity of the changes in levels of Fos was shown by a lack of any consistent difference in levels in six control sites.The present results reveal a group of anatomically related structures that work together in the intact rat brain during tasks that tax allocentric spatial working memory.

Animals↗

PubMed2000

A new form of long-term depression in the perirhinal cortex.

We demonstrate a form of long-term depression (LTD) in the perirhinal cortex that relies on interaction between different glutamate receptors. Group II metabotropic glutamate (mGlu) receptors facilitated group I mGlu receptor-mediated increases in intracellular calcium. This facilitation plus NMDA receptor activation may be necessary for induction of LTD at resting membrane potentials. However, depolarization enhanced NMDA receptor function and removed the requirement of synergy between group I and group II mGlu receptors: under these conditions, activation of only NMDA and group I mGlu receptors was required for LTD. Such glutamate receptor interactions potentially provide new rules for synaptic plasticity. These forms of LTD occur in the perirhinal cortex, where long-term decreases in neuronal responsiveness may mediate recognition memory.

2-Amino-5-phosphonovalerate↗

PubMed2000

Effects of selective excitotoxic prefrontal lesions on acquisition of nonmatching- and matching-to-place in the T-maze in the rat: differential involvement of the prelimbic-infralimbic and anterior cingulate cortices in providing behavioural flexibility.

The present study investigated the contributions of the medial prefrontal cortex and its major subdivisions, the dorsal anterior cingulate (ACd) and prelimbic-infralimbic (PL) cortices, to spatial working memory and inhibitory control processes. In experiment 1, excitotoxic lesions centred in the ACd or PL cortex did not affect acquisition of a nonmatching-to-place task in the T-maze with a retention interval of 10 s. However, the same reinforced alternation task was impaired by larger prefrontal lesions that combined ACd and PL cortices. In experiment 2, new animals were trained on a matching-to-place task in the T-maze that uses a rule counter to the animals' innate bias to alternate spontaneously. Now, discrete lesions of both the ACd and PL cortices impaired acquisition, but in different ways. Both animals with PL and with ACd lesions perseverated by nonmatching for more sessions than the controls, but only the PL animals also showed a more general increase in perseveration reflected in a further, extended period of applying an inefficient response rule (e.g. always turn right) and a deficit at reversing from matching to nonmatching. Acquisition of the matching-to-place task was also impaired by combined lesions of ACd and PL cortices. Overall, whilst spatial working memory processes appear to remain intact in those animals with discrete prefrontal lesions, the present findings provide strong evidence for the differential involvement of the prelimbic-infralimbic and anterior cingulate regions in providing behavioural flexibility.

Animals↗

PubMed2000

Disconnecting hippocampal projections to the anterior thalamus produces deficits on tests of spatial memory in rats.

A disconnection procedure was used to test whether projections from the hippocampus to the anterior thalamic nuclei (AT), via the fimbria-fornix (FX), form functional components of a spatial memory system. The behavioural effects of combined unilateral lesions in the AT and FX were compared when they were either in contralateral hemispheres (AT-FX Contra) or the same hemisphere (AT-FX Ipsi). Other groups received bilateral FX lesions and Sham surgeries. Expt 1 demonstrated that none of these lesions affected performance of an object recognition task, while performance of an object location task, which tests the subjects' preference for an object that has changed location, was impaired in the AT-FX Contra and FX groups. In a T-maze alternation task, however, the FX group was severely impaired while both the AT-FX Ipsi and AT-FX Contra lesion groups showed only a mild impairment. In order to test whether spared crossed projections might support spatial performance in the AT-FX Contra group we then examined the effects of a combined AT-FX Contra lesion coupled with transection of the hippocampal commissure. This combination of lesions produced a severe disruption in spatial memory performance in the water maze, radial arm maze and T-maze, which was significantly greater than that produced by ipsilateral and contralateral AT-FX lesions alone. These results support the notion that disconnection of the AT from their hippocampal inputs produces impairments on a range of spatial memory tasks, but indicate that there are an array of different routes that can subserve this function.

Animals↗

PubMed2000

Differential cognitive effects of colloid cysts in the third ventricle that spare or compromise the fornix.

A series of twelve cases, all of whom had received surgery for the removal of a colloid cyst in the third ventricle, was examined on a series of memory tests. The only consistent predictor of poor memory performance that could be detected from MRIs was the presence of bilateral interruption of the fornix, which occurred in three of the subjects. Although these three cases were poor on tests of learning and recall, there was evidence that recognition was less impaired. The subjects were also tested on a set of recognition and concurrent discriminations that closely matched tests given to non-human primates. Clear parallels were found between the apparent effects of fornix damage in these clinical cases and those observed following more selective surgery in non-human primates. These findings not only indicate that fornix damage is sufficient to induce anterograde amnesia but also support the validity of recent animal tests that are thought to capture aspects of episodic memory.

Adult↗

PubMed1999

Different contributions of the hippocampus and perirhinal cortex to recognition memory.

Brain regions involved in visual recognition memory, including the hippocampus, have been investigated by measuring differential neuronal activation produced by novel and familiar pictures. Novel and familiar pictures were presented simultaneously, one to each eye, using a paired viewing procedure. Differential neuronal activation was determined using immunohistochemistry for the protein products of c-fos as an imaging technique. The results establish that the regions of the rat brain associated with discriminating the novelty or familiarity of an individual item (such as a single object) differ from those responding to a spatial array of items (such as a scene). Perirhinal cortex and area TE of the temporal lobe are activated significantly more by pictures of novel than of familiar individual objects, but the hippocampus is not differentially activated. In contrast, pictures of novel arrangements of familiar items produce significantly greater activation than familiar arrangements of these items in postrhinal cortex and subfield CA1 of the hippocampus but significantly less activation in the dentate gyrus and subiculum; perirhinal cortex and area TE are not differentially activated. Thus, the hippocampus is importantly involved in processing information essential to recognition memory concerning the relative familiarity of arrangements of items, as needed for episodic memory of scenes, whereas the perirhinal cortex processes such information for individual items.

Animals↗

PubMed1999

Functionally dissociating aspects of event memory: the effects of combined perirhinal and postrhinal cortex lesions on object and place memory in the rat.

Reciprocal interactions between the hippocampus and the perirhinal and parahippocampal cortices form core components of a proposed temporal lobe memory system. For this reason, the involvement of the hippocampus in event memory is thought to depend on its connections with these cortical areas. Contrary to these predictions, we found that NMDA-induced lesions of the putative rat homologs of these cortical areas (perirhinal plus postrhinal cortices) did not impair performance on two allocentric spatial tasks highly sensitive to hippocampal dysfunction. Remarkably, for one of the tasks there was evidence of a facilitation of performance. The same cortical lesions did, however, disrupt spontaneous object recognition and object discrimination reversal learning but spared initial acquisition of the discrimination. This pattern of results reveals important dissociations between different aspects of memory within the temporal lobe. Furthermore, it shows that the perirhinal-postrhinal cortex is not a necessary route for spatial information reaching the hippocampus and that object familiarity-novelty detection depends on different neural substrates than do other aspects of event memory.

Animals↗

PubMed1999

A comparison of egocentric and allocentric spatial memory in medial temporal lobe and Korsakoff amnesics.

Two patients with medial temporal lobe damage, seven Korsakoff amnesics and fourteen healthy control subjects were tested on three conditions of a spatial memory test ('short delay', 'allocentric' and 'egocentric'). The task required subjects to recall the position of a single spot of light presented on a board after various delays. The 'short delay' condition tested memory over very short, unfilled intervals. The other two conditions used longer, filled delays. The allocentric condition required subjects to move to a different place around the board before recalling the position of the light. In the egocentric condition stimuli were presented in darkness, which eliminated allocentric cues. The Korsakoff amnesics were impaired at all delays of the short delay tasks, suggesting poor encoding. On the allocentric and egocentric tasks the Korsakoff amnesics showed a comparable impairment in the two conditions, which worsened with delay. This accelerated forgetting suggested that the Korsakoff amnesics also had impaired memory for allocentric and egocentric information. The patients with medial temporal lobe damage were unimpaired in the 'short delay' condition suggesting intact encoding and short-term memory of spatial information. However, they were impaired in the allocentric condition and showed accelerated loss of allocentric spatial information. In the egocentric condition, while the performance of one patient was impaired, the performance of the other was as good as controls. This result suggests that, in contrast to allocentric spatial memory, which is sensitive to medial temporal lobe damage, an intact medial temporal lobe need not be necessary for successful performance on an egocentric spatial memory task.

Aged↗

PubMed1999

Differential deficits in the Morris water maze following cytotoxic lesions of the anterior thalamus and fornix transection.

Rats with complete fornix lesions or cytotoxic lesions placed in the anterior thalamic region were trained on an allocentric spatial memory test (the Morris water maze). While both lesions led to impairments in locating the hidden platform in this test of reference memory, the thalamic lesions led to a significantly greater deficit than that observed after fornix transection as measured by a number of performance indices. The lesions also led to different patterns of swim behaviour in the pool. The severity of the thalamic lesion deficit was associated with anterior thalamic nuclei damage but not with damage to the nucleus medialis dorsalis. Both the fornix and the thalamic lesions also severely impaired T-maze alternation. In contrast, neither set of lesions appeared to affect the recognition of small or large objects. While the study provides further evidence of a close functional relationship between the hippocampus and the anterior thalamic nuclei, it also shows that disconnection of the fornical inputs to the anterior thalamic nuclei does not provide a full explanation of the thalamic deficit.

Animals↗

PubMed1999

Extending the spontaneous preference test of recognition: evidence of object-location and object-context recognition.

The natural preference for novel objects which is displayed by rats has been used as a behavioural index to test object recognition. In this series of experiments the standard spontaneous recognition task was extended to look at other types of recognition memory; memory for place (recognition that an object is in a location where previously there had been no object), memory for object in place (recognition that a specific object has changed position with another object) and memory for context (recognition that a familiar object is in a context different to that in which it was previously encountered). We also included a standard test of object recognition in which successful discrimination relied primarily on visual cues. In addition, we looked at how the differential exploration of objects varied within the 3 min of the test phase. The results showed that rats were sensitive to the changes made in all of the test conditions and that the level of discrimination varied within the 3 min test phase. In the standard condition and the context condition, the first 2 min were found to be the most sensitive period. In the two conditions involving a position change, discrimination was only evident in the first minute.

Animals↗

PubMed1999

Synaptic depression induced by pharmacological activation of metabotropic glutamate receptors in the perirhinal cortex in vitro.

The perirhinal cortex is crucially involved in various forms of learning and memory. Decrements in neuronal responsiveness occur in the perirhinal cortex with stimulus repetition during visual recognition performance. However, very little is known concerning the underlying mechanisms of synaptic transmission and plasticity in this cortical region. In this study, we provide evidence demonstrating the presence of functional group I, II and III metabotropic glutamate receptors in the rat perirhinal cortex in vitro. Furthermore, the results demonstrate long-lasting synaptic depression in the perirhinal cortex. Extracellular synaptic responses were recorded from superficial layers of the perirhinal cortex directly below the rhinal sulcus, in response to electrical stimuli delivered in the superficial or intermediate layers to the entorhinal or temporal cortex sides of the rhinal sulcus. Evoked synaptic potentials were depressed during bath perfusion of each of the following: the broad-spectrum metabotropic glutamate receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid, the selective group I agonist (R,S)-3,5-dihydroxyphenylglycine, the group II agonist (2S,1'R,2'R,3'R)-(2',3'-dicarboxycyclopropyl)glycine and the group III agonist (S)-2-amino-4-phosphonobutanoate. Furthermore, there was a long-lasting depression of synaptic transmission following washout of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid, (R,S)-3,5-dihydroxyphenylglycine or (2S,1'R,2'R,3'R)-(2',3'-dicarboxy-cyclopropyl)glycine. Activation of group III metabotropic glutamate receptors by (S)-2-amino-4-phosphonobutanoate did not result in long-lasting changes in synaptic transmission. Thus, the pharmacological activation of metabotropic glutamate receptors can produce short- or long-term changes in synaptic transmission in the perirhinal cortex. It is possible therefore, that metabotropic glutamate receptors are involved in the decrement in neuronal responsiveness associated with visual recognition in the perirhinal cortex.

Animals↗

PubMed1999

Does pretraining spare the spatial deficit associated with anterior thalamic damage in rats?

Rats that had been pretrained on 2 tests of allocentric memory (water maze and T maze) received bilateral cytotoxic lesions in the anterior thalamic nuclei (ATN) or transection of the fimbria-fornix (FF). After surgery, both groups of rats were impaired on both tasks, although the preoperative training resulted in a rapid initial reacquisition of the water maze task. Those rats with lesions largely restricted to the ATN were impaired at a level comparable to that produced by FF lesions. This finding is consistent with a close functional relationship between the hippocampus and the ATN, necessary for the acquisition and on-line processing of allocentric spatial information but not for the maintenance/retrieval of procedural information. The rats with more extensive thalamic lesions were more impaired in both tasks and did show a loss of procedural information.

Animals↗